The virologic markers that to date have been used as secondary endpoints in most of The ACTG protocols have been shown to be inadequate. Newer techniques that are more quantitative, faster, and less expensive are necessary. Most importantly, these new markers should change with disease progression or with effective drug therapy. More rapid assays for the determination of drug sensitivity are also needed immediately as increasing numbers of patients stay on medication for prolonged periods of time. All of these assays should correlate with the clinical data obtained from the patient. Previous work in this laboratory has indicated that virtually all of the infectious HIV found in cell-free plasma is in the form of immune complexes. Infectious immune complexes are easily and efficiently precipitated from plasma with polyethylene glycol. Procedures taking advantage of these features will be developed that will: (1) improve the p24 antigen assay and make it more clinically relevant and (2) streamline drug sensitivity testing by directly screening plasma for sensitive or resistant isolates. This assay will help the clinician determine the best drug to use for a particular patient in a more appropriate amount of time (1 to 2 weeks). In addition to the development of new virologic markers the laboratory will continue to provide the required virologic support of the ACTG by performing quantitative HIV cell and plasma cultures and p24 antigen assays. The lab will also continue to participate in the development of a consensus protocol for the isolation of drug resistant isolates from cells and the determination of their clinical relevance. The long term goal of the laboratory is to investigate the role of infectious immune complexes in the natural history and pathogenesis of HIV infection.